Research Projects

This proposal is driven by our interest in discovering novel plant-derived antimalarial compounds, particularly those with mechanisms of action distinct from current clinical treatments. Malaria remains a major global health challenge, with an estimated 263 million cases and approximately 597,000 deaths worldwide in 2023 alone. The disease, caused by Plasmodium species and transmitted via female Anopheles mosquitoes, continues to pose a serious threat due to the emergence of drug-resistant parasite strains and insecticide-resistant vectors. While the use of chloroquine (CQ) and other fast-acting aminoquinolines helped control the disease for several decades, efforts to eliminate malaria have been significantly hampered by the emergence of CQ-resistant strains and insecticide resistance in mosquito vectors. A landmark advancement in antimalarial therapy was the discovery of artemisinin, a sesquiterpene lactone endoperoxide isolated from Artemisia annua L. (family: Asteraceae), which significantly improved treatment outcomes, especially for drug-resistant malaria. Due to its success against strains resistant to CQ and sulfadoxine-pyrimethamine (SP), the World Health Organization recommended Artemisinin-based Combination Therapies (ACTs) for the treatment of uncomplicated malaria. The ACTs pair artemisinin or its derivatives with longer-acting partner drugs—such as lumefantrine, amodiaquine, piperaquine, mefloquine, sulphadoxine-pyrimethamine, or pyronaridine—to ensure complete parasite clearance and reduce the likelihood of resistance development. Although several efforts towards the total synthesis of artemisinin have been made, but none have proven practical for large-scale commercial production. As a result, Artemisia annua still continues to be the primary worldwide source for this essential and life-saving antimalarial drug. In fact, artemisinin continues to be in huge global demand due to its critical role in disease management. While current manufacturing capacity is sufficient to meet present needs, production levels tend to fluctuate with market trends. In near future, the global market for artemisinin is projected to expand significantly, potentially reaching USD 677.9 million by 2034, and likewise the Indian market is currently about USD 30.15 million and is projected to reach USD 38.82 million by 2030. Besides artemisinin, A. annua synthesizes two other secondary metabolites-artemisinic acid and arteannuin B, which are considered as its biosynthetic precursors. However, alternative possible plant-based natural sources of these compounds remain largely unexplored. To address this gap, our project aims to investigate the chemical profiles of wild Artemisia species from the remote Western Himalayan regions of Kashmir and Ladakh. These regions harbor as high as 95% species of this genus (i.e., 30) recorded in India which have not yet been systematically screened for artemisinin or its biogenetic precursors. The PI has been involved in the medicinal chemistry of artemisinin and its biogenetic precursors, has sufficient quantities of artemisinin and its biogenetic precursors viz. artemisinic acid and arteannuin B to successfully complete the proposed project. The Co-PI specializes in the taxonomy of the Artemisia genus in India, with extensive field experience in Kashmir and Ladakh. Hence, the proposed multidisciplinary study with the primary objective of identification of Artemisia species growing in Kashmir and Ladakh region containing artemisinin and or its biogenetic precursors will be topical and timely, as this may lead to the identification of alternate source(s) other than Artemisia annua for the commercial scale production of the antimalarial drug, artemisinin. It is expected that the findings from this project will serve as an essential scientific baseline for translational research.